The present invention concerns an apparatus for electrical stimulation of physiologically excitable retinal nerve cells.
The invention described is primarily for an implantable retinal stimulator or visual prosthesis or bionic eye or artificial eye. That is, a system of components designed for the restoration of some visual faculties to the profoundly blind or severely vision impaired. The main objectives of the invention is to restore the differentiation between light and dark and to offer some visual input from the environment.
In many patients who are blinded by degenerative conditions whereby the photoreceptors of the retina become dysfunctional, the retinal ganglion cells can remain largely in tact. It is the objective of the retinal -stimulator to by-pass the dysfunctional photoreceptors and electronically stimulate the surviving retinal ganglion cells, eventuating the perception of a spot of light or phosphene within the brain.
The invention described herein comprises an implanted receiver/decoder/stimulator connected to a multi site electrode array implanted on, near or under the surface of the retina. Through a tuned, inductive communication circuit, power and configuration data for the receiver/stimulator is obtained from an externally worn image processor/encoder/transmitter wherein images from the environment are obtained and processed into a grid of discreet sites of varying intensity and corresponding to the electrode sites of the array. Said intensities are then scaled in stimulus charge (amplitude x duration) in accordance with the individual patient comfort parameters such that the stimulus will be both useful, painless, and safe.
Understanding of the invention will be improved by an understanding of some of the anatomy and physiology of the human eye.
The majority of the human eye is protected within the orbital cavity. The exposed section is protected in a limited fashion by various appendages such as the eyelids and brow. Surrounded by the capsule of Tenon, a thin membrane which provides isolation and facilitates movement, the eyeball is embedded within the fatty media of the orbit.
The form of the globe itself is maintained by a hard, dense and unyielding fibrous membrane called the Sclerotic Coat (sclera). Its anterior surface is covered by the Conjunctiva, a membrane which provides the white colouring and is reflected to line the inner surface of the eyelids.
Forming approximately 15% of the anterior of the globe, the Cornea is a transparent quad layer structure consisting of epithelial cells (continuous with the conjunctiva), a central fibrous structure (Substantia Propria), an elastic lamina, and endothelial cells which line the anterior chamber. The cornea is a non vascular structure and is continuous with the sclera.
Approximately 85% of the posterior of the globe is comprised by the Choroid. A thin, highly vascular membrane, the choroid is loosely connected externally to the sclera and internally to the retina. At the point of exit of the optic nerve, the choroid is relatively thick in comparison to other sections and is firmly adhered to the sclera.
The Ciliary Body is comprised of the orbiculus ciliaris, ciliary processes and the ciliary muscle. It is primarily involved with the formation of aqueous humour and in adjusting the eye to the vision of near objects (accommodation).
The orbiculus ciliaris is continuous with the choroid. It is comprised of ridges which are arranged radially and is on the order of four millimetres in width.
The ciliary processes vary between 60 and 80 in number and are similar in structure to the choroid with the exception being that the vessels are larger and are primarily longitudinal in direction.
The ciliary muscle consists of two sets of fibres, circular and radial. By drawing upon the ciliary processes, this muscle contracts and thus relaxes the suspensory ligament of the lens causing the anterior surface of the lens to become more convex.
The Iris, (Latin for rainbow) so named from the various colours observed in different individuals, is a circular curtain which is suspended within the aqueous humour immediately behind the cornea. At its centre (slightly nasal to be precise) is the pupil, a circular aperture for the transmission of light, which changes in size with contractions of the iris. The circumference of the iris is continuous with the ciliary body and is connected to the cornea""s elastic lamina by ligament.
The retina forms the interior surface of the eye from the fovea centralis which corresponds with the axis of the eye to the ora serrata near the ciliary body.
A highly complex structure, the retina consists of ten layers between the choroid at its outer surface and the vitreous humour at its inner surface. The ten layers are as follows:
Membrana limitans internaxe2x80x94the most internal layer, comprised of fibres known as the fibres of Muller.
Stratum opticumxe2x80x94a layer of nerve fibres formed by the expansion of the optic nerve.
Ganglionic layerxe2x80x94a single layer of retinal ganglion cells.
Inner molecular layerxe2x80x94a dense layer of fibrils which are interlaced with the dendrites of the ganglion cells and those of the inner nuclear layer (described below).
Inner nuclear layerxe2x80x94comprised of amnacrine, bipolar and horizontal cells.
Outer molecular layerxe2x80x94a dense layer (thinner than the inner molecular layer) of fibrils interlaced with the processes of the horizontal and bipolar cells of the previous layer and the bases of the rods and cones (described below).
Outer nuclear layerxe2x80x94comprised of clear oval nuclear bodies named the rod-granules and cone-granules. Rod-granules being the more populous.
Membrana limitans externaxe2x80x94similar to that of the membrana limitans interna, this layer is also comprised of fibres of Mxc3xcller.
Jacob""s Membranexe2x80x94the layer of rods and cones. These are the photoreceptors and will be described in more detail later.
Tapetum nigrumxe2x80x94a single layer of hexagonal epithelial cells containing pigment-granules.
Optical or Refracting Media:
Little more than water (with some small amounts of Na and Cl), aqueous humour fills the anterior chamber (bounded by the back of the cornea and the front of the iris) and the posterior chamber (bounded by the back of the iris, the ciliary body and the lens) of the eye.
Filling approximately 80% of the volume of the eye, the vitreous body is perfectly transparent. Bound within a thin and delicate membrane (membrana hyaloidea), the vitreous body is believed to be comprised of numerous laminations of nearly pure water with small amounts of salts and albumen. It is bounded by the retina, the ciliary body and the lens.
The lens is a transparent body consisting of concentric layers ranging from soft on the surface to firm towards the centre. Surrounded by a brittle but highly elastic membrane, the lens is approximately 10 mm in diameter and 4 mm in thickness.
The function of the non-retinal components of the ocular anatomy is to maintain a focused, clear image of visual stimuli fixed on the surface of the retina. As the mechanisms involved in this process are analogous to that of a photographic camera, comparisons shall be made for illustrative purposes.
Light enters the eye at the anterior surface of the cornea. It acts in much the same way as the lens of a photographic camera. Approximately two-thirds of the bending of light necessary for providing focus takes place at the air-cornea interface.
Richly supplied with nerves, the cornea is highly sensitive to touch and pain. Its cleanliness is maintained by the tear gland secretion of lubricating fluid which is swept across the surface by the eyelids. This cleaning mechanism is amplified by the presence of dust particles or other foreign objects whereby a reflex leads to blinking and the secretion of additional lubricant.
While the lens provides light bending power in addition to the cornea, its primary role is distance compensation required to maintain focus on the retinal surface. Similar to adjusting focus of a camera by changing the distance between the lens and the film, the ocular lens changes shape, more spherical for near objects, flatter for far ones, by contraction or relaxation of the ciliary muscles. The control of the ciliary muscles is a reflex dependent upon visual input and is related to the reflex which controls the synchronous turning of the eyes.
To maintain proper exposure on the film, the aperture of the camera is adjusted in size by setting the f-stop. This allows the appropriate amount of light into the camera. as In the eye, this mechanism takes place in the iris. The pupil is adjusted in size by either the contraction of the circular muscle fibres sphincter pupillae, or the tenacity of the radial elastic fibres dilator pupillae.
The human retina is part of the brain. While removed from the brain structure itself in its development, its connection is maintained through the optic nerve.
Capable of discriminating between various wavelengths thus providing recognition of colour; providing useful vision with little more than starlight; and yielding extraordinary accuracy and detail, the retina is a complex and quite unique structure of the central nervous system.
The foregoing detailed anatomical description of the retina notwithstanding, the physiological retina may be divided into three distinct layers: the photoreceptor layer; the intermediate cell layer; and the retinal ganglion layer.
Light passes through the tiered cellular structure of the retina to the photoreceptors (rods and cones) on the Jacob""s membrane located in the back of the retina, adjacent to the sclera. While this may appear to be odd as the light must pass (and undergo some distortion) through the foregoing layers in order to reach the photoreceptors, it is believed that the reason for this evolutionary phenomenon is the presence of melanin in the tapetum nigrum. This melanin is required in order to absorb light so that it is not reflected back into the refracting media and to assist in the restoration of the pigment in the receptors which is bleached by light.
The rods, the more numerous of the two types of receptors, provide vision in dim light. They do not respond to bright light. Cones on the other hand, do not respond to dim light but provide colour and fine detail vision.
In the centre of the retina, known as the fovea, only cones exist. While cones exist elsewhere within the retina, this region, approximately 500 microns in diameter, is the location where vision is the most acute.
The intermediate cell layer consists of three types of cells: bipolar, horizontal and amacrine cells. Horizontal cells pass signals from the photoreceptors to the bipolar cells which, either through amacrine cells or directly, pass signals to the retinal ganglia.
At the front of the retina lies the layer of retinal ganglia. The axons of the retinal ganglion cells pass across the surface of the retina and collect at the optic disk where they exit to form the optic nerve.
There are approximately one million retinal ganglion cells in the human eye. In contrast, there are approximately 125 million photoreceptors. This being the case, it is an obvious question to ask how resolution is maintained. At the point of regard (the point on the retina passed by a line through the centre of the eye and the apex of the cornea) there exists a one to one correspondence between photoreceptors and retinal ganglion cells. As the angle from the point of regard increases, the quantity of photoreceptors serviced by a given retinal ganglion cell also increases. This provides a corresponding and progressive loss in resolution and eventually fades to no resolution at the far periphery. By this strategy, the eye maintains high resolution where it is important (at and around the point of regard) and only rudimentary vision at the periphery where resolution is not important.
The mechanism by which photic input to the eye is translated into a perception within the brain is not fully understood. Within the eye itself, however, a cascade of events takes place which eventuates a signal or action potential being transmitted by the retinal ganglion cells, the final product of information processing within the retina, to the vision centers of the brain by way of the optic nerve which is formed collectively by the axons of the retinal ganglion cells. This cascade begins with a change in the electrical potential on the surface of the cell membrane of the photoreceptors in response to photic input of the appropriate wavelength. This change in membrane potential causes a synaptic interaction with adjacent bipolar cells which, following a change in their membrane potential, synapse with the retinal ganglion, eventuating a depolarisation thus creating an action potential along the length of its axon.
Horizontal and amacrine cells act as regulating cells. Horizontal cells enhance contrast for spatial analysis through lateral inhibition at the synapses between the photoreceptors and the bipolar cells. Amacrine cells, while involved in several activities, are thought to regulate synapses between the bipolar cells and the retinal ganglion cells to perform temporal analysis or movement detection.
In some prevalent medical conditions such as retinitis pigulentosa and age related macular degeneration, the photoreceptors of the retina are rendered dysfunctional. It has been found by histological and psychophysical testing that in most of these cases, the retinal ganglion cells and the remainder of the visual pathway remain viable. It has also been determined by psychophysical testing that electronic stimulation of the retinal ganglion cells provide the patient with the perception of a spot of light or phosphene within the spatial vicinity of the stimulation. Variation in the intensity of the perceived phosphene has been observed through variation of stimulus strength although it is unknown if this is due to variations in activity in the originally stimulated cells or due to more retinal ganglion cells being recruited to generate action potentials. Color discretion as not been reported in electronic stimulation of the retina. This is most likely due to the bypassing of the processing levels which occur normally in the retina and provide the perception of color.
The restoration of sight to the blind has been the topic of numerous investigations. As early as 1874 surgeons have been aware that electrical stimulation of the human brain is capable of producing physical or psychophysical effects. Magnetophosphenes were recognised as early as 1896. Foerster""s 1929 investigations into electrical stimulation of the occipital poles found that phosphenes could be produced through electrical stimulation.
The prosthetic vision system by Brindley and Lewin in the late 1960""s led to the concept of a visual prosthesis becoming widely accepted in the scientific community. In 1967, their system of 80 electrodes was implanted in a female volunteer, aged 52 years who had developed bilateral glaucoma. The electrodes were placed on the visual cortex and stimulated by a series of 80 receivers implanted beneath the pericranium and secured to the skull. A helmet containing 80 transmitters was placed on the head of the volunteer, each transmitter being oriented directly above its respective receiver. By radio frequency transmission, the electrical signals required to produce stimulus were transcutaneously sent via inductive coupling to the internal prosthesis. When a series of radio waves was delivered to one of the 80 receivers, the volunteer was able to see a small spot of white light.
Despite the progress achieved in Brindley and Lewin""s studies, the useful quantity of phosphenes remained low. While up to 74 of the 75 electrodes were reported to have generated a phosphene in the apparatus implanted in their second patient (see also U.S. Pat. No. 3,699,970), many of these were too far removed from the point of regard to be useful. Furthermore, the surgery required for implantation was extensive and the apparatus for stimulation large and cumbersome. While not well known at the time, the monophasic nature of the stimulus pulses was likely to cause irreversible electrochemical reactions at the electrode/tissue interface with long term stimulation. Nevertheless, Brindley""s second patient was able to identify geometric patterns and read Braille at up to 90% accuracy at a rate of seven letters per minute using the device alone.
The human visual pathway possesses at least four potential sites of neurostimulation; the retina, the optic nerve, the lateral geniculate nucleus and the visual cortex.
While stimulation of the visual cortex has shown promise, practicality remains an issue. Implantation of a cortical prosthesis requires intracranial neurosurgery. A similar argument applies to the lateral geniculate nucleus. Nevertheless, stimulation of the visual cortex or the lateral geniculate nucleus remains the only option for those with damaged optical pathways leading to these higher processing centers.
Access to the optic nerve is readily available and would appear to be a reasonable site for stimulation of the visual pathway. However, the mapping of stimuli is largely undefined.
Relatively simplified access and common surgical techniques, including the use of retinal tacks for fixation, imply that the retina is an appropriate site for placement of a stimulating apparatus.
A number of attempts have been made to restore useful vision through electrical stimulation of physiologically excitable retinal nerve cells.
Michaelson (U.S. Pat. No. 4,628,933) has proposed a system whereby photosensitive diodes or charge coupled devices are used to detect incident light focussed upon the implanted apparatus by the existing refractory media of the eye. A radiofrequency or electromagnetic system of powering the apparatus is employed.
Systems utilizing photodiode receptors powered by incident light focussed upon the device, implanted beneath the retina, have been proposed by Chow (see U.S. Pat. Nos. 5,016,633, 5,024,233, 5,397,350 and 5,556,423). As no functioning devices of this nature have been implanted in humans, the sufficiency of the incident light to generate the energy necessary to elicit a response in the retinal ganglion cells remains in question, as does the monophasic nature of the stimulus generated by photodiodes as this may cause electrode dissolution or nerve damage.
In these systems, and those like them, the processing of the visual image takes place internal to the eye. Thus, no technological changes to the system can be made without revision surgery. It is likely that direct visual images are not the most effective means of utilizing a visual prosthesis as much of the normal processing of images cast upon a functional eye takes place in the lower orders of cells such as the photoreceptor, bipolar, amacrine and horizontal cells which are bypassed by these prostheses. Pre-processing such as edge detection or feature extraction may be necessary in order to utilize a neural stimulator to convey visual information effectively in the absence of the retinal processing mechanisms.
Rizzo and Wyatt (see also Wyatt J, Rizzo J. Ocular implants for the blind. IEEE Spectrum; 1996:47-53) have proposed a stimulator chip placed upon a polyimide substrate which is powered and controlled by an external laser beam through a photodiode array (see also Wyatt J, Rizzo J. Ocular implants for the blind. IEEE Spectrum; 1996:47-53). Although none have been implanted in humans, this system has good merit but requires a rather sophisticated eye tracking system in order that the laser beam remains fixed on the target photodiode array.
Topographic mapping of stimuli upon the retina is well defined and studies by Humayun et al. (see also Humayun M, Sato Y, Propst R, de Juan E. Can visual evoked potentials be elicited electrically despite severe retinal degeneration and markedly reduced elecroretinogram? Ger J Ophthalmol. 1994;4:57-84) found that the ganglion cells are capable of being stimulated by means of electrical signals delivered to the retinal basement membrane.
Humayun, de Juan and their colleagues at Johns Hopkins University have provided results which have confirmed that not only is stimulation of the human retina possible, the capability exists to detect movement and distinguish between adjacent phosphenes. They have gone on to propose a device and estimate the stimulation parameters necessary in eliciting a visual response in human patients (see also U.S. Pat. No. 5,109,844 and Humayun M S, de Juan E, Jr., et al. Visual perception elicited by electrical stimulation of retina in blind humans. Arch Ophthalmol. 1996; 114:40-6).
Successful restoration of a human sense has been achieved in the case of cochlear implants. In this instance, the lowest functioning level of the auditory pathway (the cochlea) is stimulated rather than higher levels such as the auditory nerve or the auditory brainstem (see also U.S. Pat. No. 4,419,995 by Hochmair et al. and U.S. Pat. No. 4,532,30 by Crosby et. al.). This suggests that retinal implants which target the lowest remaining functional level of the visual pathway (the retinal ganglion cells) may have similar success in the restoration of vision.
The primary aim of the invention is to restore visual sensation by electrically stimulating the retinal ganglion cells of the human retina in persons affected by degenerative diseases of the eye which have led to blindness or severe visual impairment.
In view of the absence of chronically implantable retinal stimulators capable of demonstrating effectiveness in the prior art, it is an objective of the present invention to provide a means by which chronic implantation and retinal stimulation may take place.
The present invention, an apparatus facilitating the delivery of electrical stimulation to retinal nerve cells, includes a receiver/decoder/stimulator comprising a semiconductor integrated circuit and other components hermetically sealed within a capsule, implanted and fixed within the eye of the patient such that it may receive power, and decode information from an externally worn image processor/encoder/transmitter through a tuned, inductive communication link and deliver controlled, charge balanced, diphasic, constant current stimulus pulses to discreet metallic electrodes on a flexible, multiple site electrode array implanted on, near or under the surface of the retina.
Said image processor comprises a means of obtaining an image, processing the image into an array of discreet pixels of variable intensity and encoding said pixel information into a series of discreet data bursts, transmitted to the receiver/decoder/stimulator, representing the chosen current amplitude, pulse duration, stimulating electrode or electrodes, and reference electrode or electrodes.
A Radio Frequency (RF) data and power trans-tissue, inductive link between the external image processor/encoder/transmitter and the internal receiver/decoder/stimulator provides for flexibility in the external image processing system such that future enhancements in processing techniques shall not require revision surgery or modification to the implanted receiver/decoder/stimulator and eliminates the need for maintenance of an internal power source such as a battery.
As chronic implantation requires, the apparatus is shaped in such a way as to provide comfort to the patient. All tissue contacting components and those components capable of exposure to tissue by way of leeching, etc. may be fabricated from materials known to be well tolerated by human tissue. Electronic circuitry required to power or control the apparatus is safely encapsulated within a hermetic chamber thereby protecting the patient from tissue-incompatible materials found in modem electronic components in addition to facilitating the presence of electronic circuitry within the corrosive environment of bodily fluids.
The circuitry of the receiver/decoder/stimulator possesses a means of excluding the delivery of a stimulation signal in the event that the encoded information received violates a pre-determined data protocol. This prevents erroneously encoded stimulus pulses from being delivered to the patient.
A common approach of insuring a charged balanced stimulus waveform in neural stimulation is to place a capacitor in series with each electrode such that no net DC current will pass. The present invention, in addition to using balanced, diphasic stimulus waveforms, employs a technique that reduces the quantity of capacitors necessary to insure charge balance from one capacitor per electrode to a total of two capacitors thus significantly reducing the size of the apparatus by reducing the quantity of components.
The apparatus is capable of delivering the aforesaid stimulus waveforms to a plurality of electrode sites. The circuitry of the receiver/decoder/stimulator differentiates the electrodes into two distinct blocks, active and indifferent. The role of these blocks can be transposed by the data sent to the device from the image processor/encoder/transmitter such that stimulus can be delivered by any one electrode in either block and the return path for the electrical signal may be passed through any one or more electrodes in the opposing block.
The apparatus possesses a means, external to the patient, of receiving data from the implanted receiver/decoder/stimulator such that the fall in electrical potential across the stimulation circuit may be derived. This, in addition to the programmable current amplitude shall facilitate the determination of the tissue impedance through which the stimulus has passed.
Maintenance of position of the implanted receiver/decoder/stimulator is, either in whole or in part, achieved by fixation of magnetic material, such as a hermetically sealed, rare earth magnet or ferromagnetic material within the external fatty media which surrounds the eye. Within the receiver/decoder/stimulator exists magnetic material which is attracted to said material in the fatty media thus achieving a mutual attraction between the internal receiver/decoder/stimulator and the material in the fatty media.